Human blood plasma contains proteins serving many different functions including transport of lipids, hormones, vitamins and minerals in the circulatory system, regulation of acellular activity and functioning of the immune system and further function as enzymes, complement components, protease inhibitors and more.
Cohn fractionation process, initially developed by Edwin Joseph Cohn, is a process that includes series of purification steps which was originally developed for extracting albumin from blood plasma. Later the process was modified to purify other plasma proteins such as immunoglobulins, coagulation factors, and Alpha-1 Antitrypsin (AAT), also known as alpha-1 proteinase inhibitor. Variety of plasma ingredients are removed during the purification of this desired plasma proteins, usually regarded to as byproducts or waste.
The Cohn fractionation process includes elevation of ethanol concentration and pH decrease from the natural pH to a more acidic pH (around 4.8) and temperature decrease from room temperature to about (−)5° C. Five major fractions are precipitated during the process, with Fractions I, II, and III precipitating out at earlier stages and fractions IV, IV-1 and V each being an end product. Relatively to plasma composition, Fraction IV and Fraction IV-1 are enriched with relatively low molecular weight plasma proteins (<200 kD) including proteases, protease inhibitors and growth factors.
There is a tangible need for a large variety of skin care products for various cosmetic or medical purposes. For instance, skin care may be directed to avoiding or repairing skin damage as a result of one or more of various factors. Common examples of such factors are exposure to heat (which may result in burns), cold, drought, radiation, such as UV radiation (for example solar radiation, which may result in sun-burn), ionizing radiation (for example as a result of cancer treatment or exposure to radioactive nuclear compounds), rough surfaces (which may result in abrasion of the skin), and exposure to substances that are harmful to the skin.
For cosmetic purposes, skin care compositions may also be directed to treat or delay the visible signs of aging of the skin, e.g. by slowing down aging of the skin and/or by rejuvenating the skin, addressing various aspects including, for example, wrinkling of the skin, sagging of the skin, loss of elasticity, age spots, hyperpigmentation and the like. To achieve effective treatment, the type of skin (e.g. dry, oily, sensitive (to e.g. solar radiation or physical contact), dark, light), must be also considered when a specific skin care product is designed. In addition, there is a growing need for hypo-allergenic or even anti-allergenic skin care products.
Wounds are caused by a disruption in the structural integrity of biological tissue. The wound healing and tissue repair is a complex and dynamic process which often is inadequate or unacceptably slow. Wound healing process includes variety of biochemistry events acting in orchestrated cascade to repair the damage. The classic model of wound healing encompasses four sequential, yet overlapping, phases comprising hemostasis, inflammation, proliferation, and remodeling. The events of each phase must occur in a precise and regulated manner. The hemostasis stops the bleeding by generating blood clots. During the inflammation phase, platelet aggregation and clotting form a matrix which traps plasma proteins and blood cells to induce the influx of various types of cells. During the cellular proliferation phase, new connective or granulation tissue and blood vessels are formed. During the remodeling phase, granulation tissue is replaced by a network of collagen and elastin fibers leading to the formation of scar tissue.
Wound healing process can become impaired by patient- or wound type factors. This is especially true in certain chronic diseases such as diabetes in the elderly, and in cancer patients. Treatments of such severe sores may include applying of autologous plasma therapies. For example, platelet rich plasma is utilized for treating hard-to-heal acute and chronic wounds (Lacci et al. 2010. Yale Journal of Biology and Medicine 83:1-9; Carter et al. 2011. Eplasty 11:e38). The combination of variety of cellular and acellular plasma components was found to improve the healing process. However, the use of plasma per se is restricted to an autologous use because of immunological response against foreign antigens and potential harming viruses.
Several isolated plasma proteins such as collagen, fibrin, fibronectin, elastin, and albumin, were shown to assist in the wound healing process.
U.S. Pat. No. 5,641,483 discloses gel and cream formulations comprising human plasma fibronectin for use in promoting wound healing in humans.
U.S. Pat. No. 4,427,651 discloses a sprayable admixture comprising thrombin, stabilizing agent such as albumin, globulin and/or fibrinogen, and a fibrinolysis inhibitor. The sprayable admixture is used for accelerating hemostasis and optimizing biochemical control of wound closure.
U.S. Pat. No. 4,427,650 discloses an enriched plasma derivative for supporting wound closure and healing, containing fibrinogen and a fibrinolysis inhibitor.
U.S. Pat. No. 7,691,816 discloses pharmaceutical compositions comprising TGF-beta superfamily members and sugars for treating wounds and fibrosis.
U.S. Pat. No. 5,631,011 discloses tissue treatment composition comprising fibrin or fibrinogen and biodegradable and biocompatible polymer.
EP Patent No. 1257304 discloses a foam wound dressing, comprising albumin.
U.S. Pat. No. 6,638,909 discloses the use of alpha-1-antitrypsin compositions in wound healing process.
U.S. Pat. No. 7,399,746 discloses pharmaceutical compositions containing fragments of alpha-1 proteinase inhibitor (API) for treating wounds.
U.S. Pat. No. 8,962,813 discloses a process for manufacturing of a composition containing a purified factor for supporting wound healing, typically from blood, the factor being selected from the group consisting of Hepatocyte Growth Factor (HGF), platelet derived growth factor (PDGF), Epidermal growth factor (EGF), transforming growth factor alpha (TGF-α), Transforming growth factor beta (TGF-β), insulin like growth factor (IGF-I) and Fibroblast growth factor (FGF). The manufacturing process comprises purification steps which are performed in the presence of antithrombin III (AT-III).
For the purpose of deriving therapeutic components from blood plasma, a large number of fresh or frozen plasma units are pooled together from various donors. Human plasma proteins for therapeutic use have been manufactured from large pools of plasma for over 50 years. One of the important concerns of single donor or pooled plasma, however, is viral safety. Though every donor who contributes to the pool of plasma is tested individually for viruses, including HIV, HBV, HCV, etc., before blood or plasma donation, there remains a small risk of infection with viruses due to “window period donations,” that is donations made between the initial acquisition of infection and the detection of a positive test result with existing diagnostics due to inherent technical limitations. Even a single donor infected with a pathogen, which remained undetected after screening, can potentially contaminate an entire pool of plasma and infect many or all recipients exposed to the pool. Therefore, there is a need to address the viral safety of pooled plasma or the therapeutic proteins derived therefrom.
Although several plasma-derived proteins are known to have wound healing effect, there is a need for additional allogeneic, standardized, hypoallergenic wound healing compositions providing sufficient efficacy together with viral safety and high patient tolerance. Additionally, there is a need for innovative compositions effective in skin care providing protection to the skin and improving its appearance.